Traditional Chinese medicine composition for treating arrhythmia and preparation method thereof

Abstract

The invention relates to a traditional Chinese medicine composition for treating arrhythmia and a preparation method thereof. The traditional Chinese medicine composition is prepared from the following active ingredients in parts by weight: 28-32 parts of a codonopsis pilosula extract, 37-43 parts of a rhizoma polygonati extract, 4-8 parts of a pseudo-ginseng extract, 3-5 parts of amber and 18-22 parts of a rhizoma nardostachyos extract. The traditional Chinese medicine composition has the advantages of high content of active ingredients and stable quality. The preparation method is scientific and feasible in process, high in extraction efficiency and good in market application prospect.

Description

Technical Field

[0001] The invention relates to a traditional Chinese medicine composition for treating arrhythmia and a preparation method thereof, belonging to the technical field of traditional Chinese medicines. Background Art

[0002] In recent years, with the aging of Chinese society, the incidence of senile arrhythmia has shown a trend of increasing year by year. Arrhythmia is caused by cardiac conduction disorder, and its clinical manifestations are: chest tightness, shortness of breath, palpitations, abnormal heart rhythm, etc. Arrhythmia belongs to critical and severe diseases, and usually the drugs are mainly antiarrhythmic drugs. Although the above drugs can improve the clinical symptoms of patients, the toxic and side effects of patients after treatment are high. Traditional Chinese medicine has obvious advantages in treating the above diseases. The Chinese medicine composition for treating arrhythmia diseases described in the present invention is Wenxin Granule, which is prepared from Chinese medicinal materials such as Codonopsis pilosula, Polygonatum sibiricum, Panax notoginseng, Amber, and Nardostachys grandiflora. It has the effects of invigorating qi and nourishing yin, promoting blood circulation and removing blood stasis, and can be used for palpitations and restlessness caused by qi and yin deficiency, heart vessel stasis, shortness of breath and fatigue, and can be used for symptoms such as chest tightness and chest pain, and ventricular premature beats.

[0003] The applicant of the present invention has previously applied for multiple patent applications for the product, with application numbers: 01131734.5 (a Chinese medicine for treating arrhythmia and its preparation method), 200410081398.2 (a Chinese medicine preparation for treating arrhythmia and its preparation method), 200530090041.6 (drug packaging box), 200610042976.0 (preparation method and quality control method), 200610042974.1 (quality inspection standard method), 200810232536.0 (application for preventing and treating allergic diseases), 200810183930 .X (application in fracture drugs), 201510145198.7 (detection method of volatile components in Wenxin granules), 201610013406.2 (high performance liquid chromatography detection method), 201811308826.9 (application of dangshen glycoside analogous compounds in the preparation of drugs for the treatment of arrhythmia), 201910483321.4 (isomaranth-type diterpene compounds and preparation methods thereof), 202210084515.9 (detection method of Wenxin traditional Chinese medicine composition), 202210355751.X (detection of volatile components of nardus strychnifolia and fingerprint construction method).

[0004] The applicant of the present invention systematically combed through the prior art literature of the product and found that the quality standard of Wenxin Granule recorded in the 2020 edition of the Chinese Pharmacopoeia is: Each bag contains notoginseng, calculated by the total amount of notoginseng saponin R1 (C47H80O18), ginsenoside Rg1 and ginsenoside Rb1, which shall not be less than 17.0 mg. Usage and dosage: Take with boiled water. 1 bag at a time, 9g / bag, 3 times a day. The preparation process of the product is as follows: amber is crushed into fine powder, volatile oil is extracted from nard, and the aqueous solution is collected after extraction; Panax notoginseng is crushed into coarse powder, extracted twice with 80% ethanol by reflux, each time for 2 hours, filtered, the filtrates are combined, and concentrated under reduced pressure to a clear paste, the residues are decocted with water twice, the first time for 2 hours and the second time for 1.5 hours, and the decoctions are combined: Codonopsis pilosula and Polygonatum sibiricum are decocted with water twice, the decoctions are combined with the above decoctions, and filtered; the filtrate is concentrated to a relative density of a clear paste, ethanol is added to make the alcohol content reach 65%, stirred, allowed to stand for 24 hours, filtered, the filtrate is concentrated under reduced pressure to a thick paste, combined with Panax notoginseng clear paste, and mixed. Add the above-mentioned amber fine powder, sucrose, beta-cyclodextrin, aspartame, and dextrin, mix well, granulate, dry, spray with volatile oil of nard, mix well, and make granules; or add the above-mentioned amber fine powder, aspartame, dextrin and appropriate amount of soluble starch, mix well, granulate, dry, spray with volatile oil of nard, mix well, and make granules without sucrose.

[0005] Wenxin Granule has a good reputation in the market of traditional Chinese medicine for the treatment of arrhythmia. The market sales of this product have also increased year by year. However, the medicinal materials contained in this product are all precious medicinal materials, such as nard, amber, polygonatum, panax notoginseng, and codonopsis, and nard and amber are rare varieties of traditional Chinese medicine. The resources of the above medicinal materials are very scarce.

[0006] How to improve the enrichment and utilization rate of the effective ingredients of the above-mentioned medicinal materials to solve the increasingly tense problem of Chinese medicinal materials resources is urgent. However, in the actual clinical application of the Chinese medicine composition, the dosage of the medicine taken each time is too large, which brings inconvenience to some elderly patients and also causes great resource loss. Therefore, we found that the clinical effect of the Chinese medicine preparation prepared by the above-mentioned preparation method needs to be further optimized and improved. It is particularly urgent to research and develop a Chinese medicine preparation with better efficacy and higher enrichment of effective ingredients. Summary of the invention

[0007] The object of the present invention is to provide a Chinese medicine composition for treating arrhythmia and a preparation method thereof. The Chinese medicine composition has reliable clinical efficacy, high enrichment of effective ingredients, can greatly reduce the dosage taken by patients, can also save raw material costs, and improve the utilization rate of medicinal resources.

[0008] The Chinese medicine composition of the present invention comprises: codonopsis pilosula extract, polygonatum sibiricum extract, notoginseng extract and nard extract, which has the advantages of high content of effective substances and stable quality. The preparation method is scientific and feasible, has high extraction efficiency and has good market application prospects.

[0009] The technical solution of the present invention is:

[0010] A traditional Chinese medicine composition for treating arrhythmia, the traditional Chinese medicine composition is composed of active ingredients in the following weight ratio: 28-32 parts of Codonopsis pilosula extract, 37-43 parts of Polygonatum sibiricum extract, 4-8 parts of Panax notoginseng extract, 3-5 parts of amber, and 18-22 parts of Nardostachys chinensis extract.

[0011] The preferred Chinese medicine composition of the present invention is composed of active ingredients in the following weight ratio: 30 parts of Codonopsis pilosula extract, 30 parts of Polygonatum sibiricum extract, 60 parts of Panax notoginseng extract, 4 parts of amber, and 20 parts of Nardostachys grandiflora extract.

[0012] As a preferred embodiment of the present invention, the content of the Codonopsis pilosula extract is ≥50%, and the active ingredients of the Codonopsis pilosula extract include: a mixture of one or more ingredients of Codonopsis pilosula polysaccharide, Codonopsis pilosula saponins, and Codonopsis pilosula acetyl glucoside.

[0013] As a preferred embodiment of the present invention, the content of the polygonatum sibiricum extract is ≥50%, and the active ingredients of the polygonatum sibiricum extract include: a mixture of one or more components of polygonatum sibiricum polysaccharide, polygonatum sibiricum saponin, and polygonatum sibiricum polyphenol.

[0014] As a preferred embodiment of the present invention, the content of the Panax notoginseng extract is ≥60%, and the active ingredients of the Panax notoginseng extract include: a mixture of one or more components of notoginseng saponins, ginsenoside Rg1, ginsenoside Rb1, ginsenoside Rd, Panax notoginseng polysaccharides, volatile oils, amino acids, and total polysaccharides.

[0015] As a preferred embodiment of the present invention, the content of the nardostachys extract is ≥40%, and the active ingredients of the nardostachys extract include: a mixture of one or more ingredients of flavonoids, polysaccharides, volatile oils, triterpenes, phenols, coumarins, and nardostachys ketone.

[0016] As a preferred embodiment of the present invention, the preparation method of the Codonopsis pilosula extract is as follows: take Codonopsis pilosula medicinal material, add water in an amount of 7 to 11 times the weight ratio of the medicinal material, add 0.05 to 1.5% of cellulase, heat to 40 to 55°C, extract 1 to 2 times, each enzymatic hydrolysis time is 0.5 to 1.5 hours, filter, combine the filtrates, concentrate the filtrates into a clear paste, add ethanol to make the alcohol content reach 60 to 75%, stir, let stand for 8 to 24 hours, filter, and reduce the pressure on the filtrate to concentrate it into a dry paste powder to obtain the Codonopsis pilosula extract.

[0017] As a further preferred embodiment of the present invention, the preparation method of the polygonatum extract is: take polygonatum medicinal material, add water in an amount of 8 to 12 times the weight ratio of the medicinal material, heat and decoct twice, each decoction interval is 1 hour, filter, combine the filtrates, and concentrate the filtrates to a polygonatum extract clear paste with a relative density of 1.10 to 1.30 (60°C), select AB-8 macroporous resin, the ratio of the amount of polygonatum extract clear paste loaded to the amount of AB-8 resin is 0.3 to 0.5, the mass concentration of the loaded polygonatum extract is 0.7 to 1.2 mg / ml, the equilibrium adsorption time is 8 to 12 hours, and pure water is used to elute 3 to 5 column volumes, and the eluate of the above different concentrations of 40% to 60% ethanol-water is collected, and eluted for 3 to 6 column volumes, The eluate is collected and concentrated to obtain the polygonatum extract.

[0018] Preferably, the preparation method of the Panax notoginseng extract is: take Panax notoginseng medicinal materials, crush them into particles exceeding 20 mesh, reflux with 75-90% ethanol, add ethanol in an amount of 8-11 times the weight ratio of the medicinal materials, extract 1-3 times, each decoction time is 0.5-1.5 hours, filter, combine the filtrates, and concentrate under reduced pressure to obtain Panax notoginseng concentrate; apply D101 macroporous resin to the concentrate, rinse with water for 3-5 column volumes, then rinse with 20-40% ethanol for 4-6 column volumes, elute with 60-80% ethanol for 3-6 column volumes, collect the Panax notoginseng eluate, concentrate and dry, and obtain the Panax notoginseng extract.

[0019] Preferably, the preparation method of the nardostachys extract is: take nardostachys medicinal materials, add water in an amount of 8 to 12 times the weight ratio of the medicinal materials, extract 1 to 3 times, each decoction time is 1 to 1.5 hours, steam distill for 1 to 2 hours, collect nardostachys volatile oil, combine the above nardostachys extraction filtrate, reduce pressure and concentrate it into a clear paste, add chitosan with a mass fraction of 1.5 to 2.5%, heat and stir evenly at 55°C, refrigerate and stand for 12 hours, filter, spray dry the filtrate into a dry paste powder, sieve to obtain the nardostachys extract.

[0020] The preparation method of the Chinese medicine composition of the present invention comprises the following steps:

[0021] ⑴. Take Codonopsis pilosula, add 7-11 times the weight of the medicinal material water, add 0.05-1.5% of cellulase, heat to 40-55°C, extract 1-2 times, each enzymolysis time is 0.5-1.5h, filter, combine the filtrates, concentrate the filtrates into a clear paste, add ethanol to make the alcohol content reach 60-75%, stir, let stand for 8-24 hours, filter, and decompress the filtrate to concentrate it into a dry paste powder to obtain Codonopsis pilosula extract;

[0022] ⑵, take polygonatum sibiricum medicinal material, add 8 to 12 times of water in weight ratio of medicinal material, heat and decoct 1 to 2 times, each decoction time is 0.5 to 1.5h, filter, combine the filtrate, concentrate the filtrate to a polygonatum sibiricum extract paste with a relative density of 1.10 to 1.30 (60°C), select AB-8 macroporous resin, the ratio of the amount of polygonatum sibiricum extract paste to the amount of AB-8 resin is 0.3 to 0.5, the mass concentration of the polygonatum sibiricum extract is 0.7 to 1.2 mg / ml, the equilibrium adsorption time is 8 to 12 hours, elute with pure water for 3 to 5 column volumes, collect the eluate of the above different concentrations of 40% to 60% ethanol-water, elute for 3 to 6 column volumes, collect the eluate, and concentrate to obtain the polygonatum sibiricum extract;

[0023] ⑶. Grind the Radix Notoginseng into 20-mesh particles, reflux with 75-90% ethanol, add 8-11 times the weight of the Radix Notoginseng, extract 1-3 times, decoct for 0.5-1.5 hours each time, filter, combine the filtrates, and concentrate under reduced pressure to obtain a Radix Notoginseng concentrate; apply D101 macroporous resin to the concentrate, rinse with water for 3-5 column volumes, then rinse with 20-40% ethanol for 4-6 column volumes, elute with 60-80% ethanol for 3-6 column volumes, collect the Radix Notoginseng eluate, concentrate and dry, and obtain a Radix Notoginseng extract;

[0024] (4) Ultrafine grinding of amber into fine powder of 100-200 nm;

[0025] ⑸. Take the medicinal material of Nardostachys grandiflora, add 8 to 12 times the weight of the medicinal material of water, extract 1 to 3 times, each decoction time is 1 to 1.5 hours, steam distill for 1 to 2 hours, collect the volatile oil of Nardostachys grandiflora, combine the above Nardostachys grandiflora extraction filtrate, decompress and concentrate to a clear paste, add 1.5 to 2.5% chitosan by mass fraction, heat and stir evenly at 55°C, refrigerate and stand for 12 hours, filter, spray dry the filtrate to a dry paste powder, sieve, and obtain the Nardostachys grandiflora extract;

[0026] (6) Take the Codonopsis pilosula extract in step (1), the Polygonatum sibiricum extract in step (2), the Panax notoginseng extract in step (3), the amber ultrafine powder in step (4), the Nardostachys grandiflora extract and volatile oil in step (5), mix them well, and add pharmaceutical excipients to prepare various oral preparations.

[0027] Further preferably, the preparation method of the Chinese medicine composition of the present invention comprises the following steps:

[0028] ⑴. Take Codonopsis pilosula, add 10 times the weight of water, add 1% of cellulase, heat to 50°C, extract twice, each enzymolysis time is 1h, filter, combine the filtrates, concentrate the filtrates into a clear paste, add ethanol to make the alcohol content reach 70%, stir, let stand for 12 hours, filter, and decompress the filtrate to concentrate it into a dry paste powder to obtain Codonopsis pilosula extract;

[0029] ⑵, take polygonatum sibiricum medicinal material, add 10 times of water in weight ratio of medicinal material, heat and decoct for 2 times, each decoction interval is 1h, filter, combine the filtrate, concentrate the filtrate to a polygonatum sibiricum extract paste with a relative density of 1.10-1.30 (60°C), select AB-8 macroporous resin, the ratio of the amount of polygonatum sibiricum extract paste to the amount of AB-8 resin is 0.3-0.5, the mass concentration of the loaded polygonatum sibiricum extract is 0.7-1.2 mg / ml, the equilibrium adsorption time is 8-12 hours, elute with pure water for 3-5 column volumes, collect the eluate of the above different concentrations of 40%-60% ethanol-water, elute for 3-6 column volumes, collect the eluate, and concentrate to obtain the polygonatum sibiricum extract;

[0030] ⑶. Grind the Radix Notoginseng into 20-mesh particles, reflux with 80% ethanol, add 10 times the weight of the Radix Notoginseng ethanol, extract twice, decoct for 1 hour each time, filter, combine the filtrates, and concentrate under reduced pressure to obtain a Radix Notoginseng concentrate; apply D101 macroporous resin to the concentrate, rinse with water for 4 column volumes, then rinse with 30% ethanol for 6 column volumes, elute with 60-80% ethanol for 6 column volumes, collect the Radix Notoginseng eluate, concentrate and dry, and obtain the Radix Notoginseng extract;

[0031] (4) Ultrafine grinding of amber into fine powder of 100-200 nm;

[0032] ⑸. Take the medicinal material of Nardostachys grandiflora, add 9 times the weight of the medicinal material water, extract twice, each decoction time is 1 hour, steam distill for 1.5 hours, collect the volatile oil of Nardostachys grandiflora, combine the above Nardostachys grandiflora extraction filtrate, reduce pressure and concentrate it into a clear paste, add 2% chitosan by mass fraction, heat and stir evenly at 55°C, refrigerate and stand for 12 hours, filter, spray dry the filtrate into a dry paste powder, sieve to obtain the Nardostachys grandiflora extract.

[0033] (6) Take the Codonopsis pilosula extract in step (1), the Polygonatum sibiricum extract in step (2), the Panax notoginseng extract in step (3), the amber ultrafine powder in step (4), the Nardostachys grandiflora extract and volatile oil in step (5), mix them well, and add pharmaceutical excipients to prepare various oral preparations.

[0034] The novel preparation process technology of the present invention can also be made into different oral Chinese medicine preparations such as granules, capsules, tablets or pills to meet the medication needs of different types of patients.

[0035] Granules: The traditional Chinese medicine mixture prepared by the present invention is mixed with appropriate amounts of beta-cyclodextrin, aspartame, dextrin, starch, lactose, mannitol, sodium carboxymethyl starch and microcrystalline cellulose, granulated, dried, and mixed to prepare granules.

[0036] Capsules: Add appropriate auxiliary materials, such as calcium dihydrogen phosphate, sodium carboxymethyl starch, pregelatinized starch, magnesium stearate, talcum powder, and micro-powdered silica gel, to the traditional Chinese medicine mixture prepared by the present invention, granulate, and fill into capsules to prepare capsules.

[0037] Dropping pills: the Chinese medicine mixture prepared by the present invention is mixed with a suitable matrix, stearic acid, PEG4000, PEG6000, poloxamer, monostearate glyceryl, polyoxyethylene pyrrolidone insect wax, beeswax, hot melt, and the above matrix excipients, stirred evenly, and dripped to prepare dropping pills.

[0038] Tablets: The Chinese medicine mixture prepared by the present invention is mixed evenly with appropriate amounts of starch, lactose, microcrystalline cellulose, low-substituted hydroxypropyl cellulose, magnesium stearate, talcum powder, starch slurry and other auxiliary materials, granulated and pressed into tablets.

[0039] In order to further reflect the innovativeness of the preparation process technology of the present invention, a large number of previous process research and screening schemes are now organized as follows:

[0040] 1. Process optimization of Polygonatum sibiricum extract

[0041] 1.1 Orthogonal experimental design

[0042] Weigh the medicinal material of Polygonatum sibiricum, extract it by water decoction, take the extract (%) and total polysaccharide content as evaluation indicators, take the amount of water added, extraction time and number of extractions as investigation factors, carry out L9 (3 factors 3 levels) orthogonal test, and preferably investigate the best Polygonatum sibiricum extraction process conditions. Among them, the content determination adopted in the present invention is determined according to the determination method of the 2020 edition of the "Chinese Pharmacopoeia". The present invention adopts UV-visible spectrophotometry to determine the content of Polygonatum sibiricum polysaccharides.

[0043] Table 1 Orthogonal test factor level table

[0044]

[0045] Table 2 Orthogonal test results

[0046]

[0047] According to the experimental results in Table 2, the best preparation and extraction process is: 10 times the amount of water, 2 decoctions, and 60 minutes each decoction.

[0048] 1.2 Optimal Process for Purification of Polygonatum sibiricum

[0049] Take polygonatum sibiricum medicinal material, add water with a weight ratio of 10 times that of the medicinal material, heat and decoct for 2 times, each decoction interval is 1 hour, filter, combine the filtrates, and concentrate the filtrates to a polygonatum sibiricum extract paste with a relative density of 1.15 (60°C). AB-8 macroporous resin is selected, the ratio of the amount of polygonatum sibiricum extract paste loaded to the amount of AB-8 resin is 0.36, the mass concentration of the loaded polygonatum sibiricum extract is 0.9 mg / ml, the equilibrium adsorption time is 10 hours, and 4 column volumes are eluted with pure water respectively, and 5 column volumes of the eluates of the above different concentrations of 50% ethanol-water are collected respectively, and eluted for 5 column volumes, and the eluates are collected and concentrated to obtain the polygonatum sibiricum extract; the present invention is purified according to the above-mentioned optimized enrichment process, and the results are shown in Table 3.

[0050] Table 3 Verification test of extraction and purification process of Polygonatum sibiricum

[0051]

[0052]

[0053] From the results in Table 3 above, it can be seen that the preferred polygonatum purification process of the present invention has a feasible enrichment effect. The total polygonatum polysaccharide content in the polygonatum extract is 49.67% to 51.04%, and the total polygonatum saponin content is 2.87% to 3.45%. It can be seen that the extraction and purification process of the polygonatum polysaccharide components of the present invention is stable and feasible.

[0054] 2. Optimization of Codonopsis Extract Process

[0055] 2.1 Optimization of Codonopsis Extraction Process

[0056] The invention relates to the extract of Codonopsis pilosula, and the effect of water addition, decoction times and extraction time on Codonopsis pilosula saponin and Codonopsis pilosula extraction rate, and the optimal Codonopsis pilosula extraction process parameters are preferably investigated. The invention adopts HPLC method and sulfuric acid-phenol method to determine the content of Codonopsis pilosula polysaccharide. Extract yield (%) = Codonopsis pilosula extract powder / Codonopsis pilosula × 100%.

[0057] Table 4 Comparison between enzymatic hydrolysis of Codonopsis pilosula and traditional extraction process

[0058]

[0059]

[0060] As can be seen from Table 4, the enzymatic hydrolysis technology used in Experiments 4, 5, and 6 of the present invention can reduce the resistance of the mass transfer barrier of the cell wall of Codonopsis pilosula medicinal materials, dissolve the effective ingredients in Codonopsis pilosula from the cell membrane, and increase the extraction rate of Codonopsis pilosula polysaccharides (35.14% to 38.57%) and the content of Codonopsis pilosula polysaccharides in the extract (7.69 to 8.38 mg / g).

[0061] 2.2 Extraction and purification process of Codonopsis pilosula

[0062] Take Codonopsis pilosula medicinal material, add water in a weight ratio of 10 times the weight of the medicinal material, add 1% of cellulase, heat to 50°C, extract twice, each enzymolysis time is 1 hour, filter, combine the filtrates, concentrate the filtrates into a clear paste, add ethanol to make the alcohol content reach 70%, stir, let stand for 12 hours, filter, and decompress the filtrate to concentrate it into a dry paste powder to obtain a Codonopsis pilosula extract; content detection shows that the Codonopsis pilosula extract of the present invention has a total polysaccharide content of 45.35%, a total saponin content of 6.29%, and a codonopsis glycoside content of 1.98%.

[0063] 3. Process Optimization of Panax Notoginseng Extract

[0064] The medicinal material of Panax notoginseng is crushed into particles with a diameter of 20 mesh, refluxed with 80% ethanol, extracted twice, each decoction time is 1 hour, filtered, the filtrates are combined, and concentrated under reduced pressure to obtain a Panax notoginseng concentrate; the concentrate is applied to a D101 macroporous resin, washed with water for 4 column volumes, then washed with 30% ethanol for 6 column volumes, eluted with 60-80% ethanol for 6 column volumes, the Panax notoginseng eluate is collected, concentrated and dried to obtain a Panax notoginseng refined product; the content of the present invention is determined by high performance liquid chromatography, acetonitrile-water is selected as the mobile phase, gradient elution, detection wavelength is 203nm, injection volume is 10μL, flow rate: 1.0mL·min -1 The total content of notoginsenoside R1, ginsenoside Rg1, Rb1 and ginsenoside Re in the Panax notoginseng extract was determined to be more than 83.16%.

[0065] 4. Processing of Nardostachys grandiflora Extract

[0066] Take the medicinal material of Nardostachys grandiflora, add 9 times of water in the weight ratio of the medicinal material, decoct and extract twice, each decoction time is 1 hour, steam distill for 1.5 hours, collect the volatile oil of Nardostachys grandiflora, combine the above Nardostachys grandiflora extraction filtrate, decompress and concentrate into a clear paste, add chitosan with a mass fraction of 1.5-2.5%, heat and stir evenly at 50-60°C, refrigerate and stand for 8-16 hours, filter, spray dry the filtrate into dry paste powder, sieve, and obtain the Nardostachys grandiflora extract. According to the content determination, the Nardostachys grandiflora extract contains 23.3% of Nardostachys grandiflora flavonoids, 12.1% of Nardostachys grandiflora polysaccharides, 3.8% of Nardostachys grandiflora triterpenes, and 2.6% of Nardostachys grandiflora phenols.

[0067] Beneficial effects of the Chinese medicine composition of the present invention

[0068] ⑴. The innovation of the present invention is to provide a Chinese medicine composition with a high content of effective substances, which specifically includes the following: ①. The extraction and purification process of polygonatum is optimized, and the total polysaccharide content of polygonatum contained in the polygonatum extract is finally obtained to be 49.67% to 51.04%, and the total saponin content of polygonatum is 2.87% to 3.45%. ②. The process of extracting Codonopsis pilosula is optimized. The present invention adopts the enzymatic hydrolysis method of Codonopsis pilosula, and can reduce the mass transfer barrier resistance of the cell wall of Codonopsis pilosula medicinal material, so that the effective ingredients in Codonopsis pilosula are completely dissolved from the cell membrane, which can improve the extraction rate of Codonopsis pilosula polysaccharide (22.14% to 23.57%) and the content of Codonopsis pilosula polysaccharide in the extract (7.69 to 8.38 mg / g). ③. Process optimization of Panax notoginseng extract. The present invention adopts macroporous resin elution purification technology to improve the content of effective ingredients in Panax notoginseng extract. Among them, the total content of Panax notoginseng saponin R1, ginsenoside Rg1, Rb1, and ginsenoside Re in Panax notoginseng extract prepared by the best process is more than 83.16%. ④. Process optimization of Nardostachys chinensis extract. The present invention also adopts chitosan purification process technology to enrich the effective substance components in Nardostachys chinensis extract, and finally obtains 23.3% of Nardostachys chinensis flavonoids, 12.1% of Nardostachys chinensis polysaccharides, 3.8% of Nardostachys chinensis triterpenes, and 2.6% of Nardostachys chinensis phenols in Nardostachys chinensis extract.

[0069] (2) Pharmacological experiments show that the Chinese medicine composition of the present invention can significantly delay the onset of arrhythmia in rats induced by barium chloride solution and shorten its duration. This further confirms that the Chinese medicine composition of the present invention has a strong protective effect against arrhythmia. DETAILED DESCRIPTION

[0070] The following are specific embodiments of the present invention, which are used to illustrate the technical solutions to the technical problems to be solved in this application document and help those skilled in the art to understand the present invention. However, the implementation of the technical solutions of the present invention is not limited to these embodiments.

[0071] Example 1 Preparation of the Chinese medicine composition granules of the present invention

[0072] ⑴. Take 300g of Codonopsis pilosula, add 10 times the weight of water, add 1% of cellulase, heat to 50°C, extract twice, each enzymolysis time is 1h, filter, combine the filtrates, concentrate the filtrates into a clear paste, add ethanol to make the alcohol content reach 70%, stir, let stand for 12 hours, filter, and decompress the filtrate to concentrate it into a dry paste powder to obtain Codonopsis pilosula extract;

[0073] ⑵, take 400g of polygonatum, add 10 times the weight of water, heat and decoct twice, each decoction interval is 1h, filter, combine the filtrates, concentrate the filtrates to a polygonatum extract paste with a relative density of 1.10-1.30 (60°C), select AB-8 macroporous resin, the ratio of the amount of polygonatum extract paste loaded to the amount of AB-8 resin is 0.4, the mass concentration of the loaded polygonatum extract is 1mg / ml, the equilibrium adsorption time is 10 hours, elute with pure water for 3-5 column volumes, collect the eluates of the above different concentrations of 60% ethanol-water, elute for 5 column volumes, collect the eluates, and concentrate to obtain the polygonatum extract;

[0074] ⑶, take 60g of Panax notoginseng, crush it into 20 mesh particles, reflux with 80% ethanol, add 10 times the weight of the medicinal material ethanol, extract twice, each decoction time is 1 hour, filter, combine the filtrates, and concentrate under reduced pressure to obtain Panax notoginseng concentrate; apply D101 macroporous resin to the concentrate, rinse with water for 4 column volumes, then rinse with 30% ethanol for 6 column volumes, elute with 60% ethanol for 6 column volumes, collect the Panax notoginseng eluate, concentrate and dry, and obtain the Panax notoginseng extract;

[0075] (4) Grind 40g of amber into 100-200nm fine powder by ultrafine grinding;

[0076] ⑸. Take 200g of Nardostachys serrata, add 9 times the weight of the medicinal material water, extract twice, decoct for 1 hour each time, steam distill for 1.5 hours, collect the volatile oil of Nardostachys serrata, combine the above Nardostachys serrata extract filtrate, decompress and concentrate to a clear paste, add 2% chitosan by mass, heat and stir at 55°C, refrigerate and stand for 12 hours, filter, spray dry the filtrate to a dry paste powder, sieve to obtain Nardostachys serrata extract;

[0077] (6) Take the Codonopsis pilosula extract in the above step (1), the Polygonatum sibiricum extract in step (2), the Panax notoginseng extract in step (3), the amber ultrafine powder in step (4), and the Nardostachys grandiflora extract in step (5), mix them evenly, spray in Nardostachys grandiflora volatile oil, add appropriate amounts of beta-cyclodextrin, aspartame, and dextrin, the ratio of the above mixture to the pharmaceutical excipients is 1: dosage, granulate, and dry to form 1000g of granules.

[0078] Example 2 Preparation of the Chinese medicine composition capsule of the present invention

[0079] ⑴, take 280g of Codonopsis pilosula, add 11 times the weight of the medicinal material water, add 0.8% of cellulase, heat to 40°C, extract once, each enzymatic hydrolysis time is 1.5h, filter, combine the filtrates, concentrate the filtrates into a clear paste, add ethanol to make the alcohol content reach 60%, stir, let stand for 8 hours, filter, and decompress the filtrate to concentrate it into a dry paste powder to obtain Codonopsis pilosula extract;

[0080] ⑵, take 430g of polygonatum, add 12 times the weight of water, heat and decoct once, each decoction time is 1.5h, filter, combine the filtrates, concentrate the filtrates to a relative density of 1.15 (60°C) polygonatum extract paste, select AB-8 macroporous resin, the ratio of the amount of polygonatum extract paste to the amount of AB-8 resin is 0.5, the mass concentration of the polygonatum extract is 0.7mg / ml, the equilibrium adsorption time is 12 hours, elute with pure water for 3 to 5 column volumes, collect the eluates of the above different concentrations of 60% ethanol-water, elute for 3 to 6 column volumes, collect the eluates, and concentrate to obtain the polygonatum extract;

[0081] ⑶, take 40g of Panax notoginseng, crush it into 20 mesh particles, reflux with 90% ethanol, add 11 times the weight of the medicinal materials ethanol, extract once, each decoction time is 1.5 hours, filter, combine the filtrate, and concentrate under reduced pressure to obtain Panax notoginseng concentrate; apply D101 macroporous resin to the concentrate, rinse with water for 3 to 5 column volumes, then rinse with 20% ethanol for 4 to 6 column volumes, elute with 60% ethanol for 3 to 6 column volumes, collect the Panax notoginseng eluate, concentrate and dry, and obtain Panax notoginseng extract;

[0082] (4) Grind 30g of amber into 100-200nm fine powder using ultrafine grinding;

[0083] ⑸. Take 220g of Nardostachys serrata, add 12 times the weight of the medicinal material water, extract once, decoct for 1.5 hours each time, steam distill for 2 hours, collect Nardostachys volatile oil, combine the above Nardostachys serrata extract filtrate, decompress and concentrate to a clear paste, add 2.5% chitosan by mass, heat and stir at 55°C, refrigerate and stand for 12 hours, filter, spray dry the filtrate to a dry paste powder, sieve to obtain Nardostachys serrata extract;

[0084] (6) Take the Codonopsis pilosula extract in step (1), the Polygonatum sibiricum extract in step (2), the Panax notoginseng extract in step (3), the amber ultrafine powder in step (4), and the Nardostachys grandiflora extract in step (5), mix them evenly, spray Nardostachys grandiflora volatile oil into them, add calcium dihydrogen phosphate, sodium carboxymethyl starch, and magnesium stearate, granulate, dry, and fill into capsules to prepare capsules.

[0085] Example 3 Preparation of the Chinese medicine composition pills of the present invention

[0086] ⑴, take 320g of Codonopsis pilosula, add 7 times the weight of the medicinal material water, add 1.1% of cellulase, heat to 55°C, extract twice, each enzymolysis time is 0.5h, filter, combine the filtrates, concentrate the filtrates into a clear paste, add ethanol to make the alcohol content reach 75%, stir, let stand for 24 hours, filter, and decompress the filtrate to concentrate it into a dry paste powder to obtain Codonopsis pilosula extract;

[0087] ⑵, take 370g of polygonatum, add 8 times of water in weight ratio of the medicinal material, heat and decoct for 2 times, each decoction time is 0.5h, filter, combine the filtrates, concentrate the filtrates to a polygonatum extract paste with a relative density of 1.10-1.30 (60°C), select AB-8 macroporous resin, the ratio of the amount of polygonatum extract paste loaded to the amount of AB-8 resin is 0.3-0.5, the mass concentration of the loaded polygonatum extract is 0.7-1.2mg / ml, the equilibrium adsorption time is 8-12 hours, elute with pure water for 3-5 column volumes, collect the eluates of the above different concentrations of 40%-60% ethanol-water, elute for 3-6 column volumes, collect the eluates, and concentrate to obtain the polygonatum extract;

[0088] ⑶, take 80g of Panax notoginseng, crush it into 20 mesh particles, reflux with 75% ethanol, add 8 times the weight of the medicinal material ethanol, extract 3 times, each decoction time is 0.5 hour, filter, combine the filtrates, and concentrate under reduced pressure to obtain Panax notoginseng concentrate; apply D101 macroporous resin to the concentrate, rinse with water for 3 to 5 column volumes, then rinse with 20 ethanol for 4 to 6 column volumes, elute with 80% ethanol for 3 to 6 column volumes, collect the Panax notoginseng eluate, concentrate and dry, and obtain Panax notoginseng extract;

[0089] (4) Grind 50g of amber into 100-200nm fine powder by ultrafine grinding;

[0090] ⑸. Take 180g of Nardostachys serrata, add 8 times the weight of the medicinal material water, extract 3 times, decoct for 1 hour each time, steam distill for 1 hour, collect Nardostachys volatile oil, combine the above Nardostachys serrata extract filtrate, decompress and concentrate to a clear paste, add 1.5% chitosan by mass, heat and stir at 55°C, refrigerate and stand for 12 hours, filter, spray dry the filtrate to a dry paste powder, sieve to obtain Nardostachys serrata extract;

[0091] (6) Take the Codonopsis pilosula extract in the above step (1), the Polygonatum sibiricum extract in step (2), the Panax notoginseng extract in step (3), the amber ultrafine powder in step (4), and the Nardostachys grandiflora extract in step (5), mix them evenly, spray in Nardostachys grandiflora volatile oil, add PEG4000, PEG6000, hot melt, and the above matrix excipients, stir evenly, and drip to make dripping pills.

[0092] Example 4 Preparation of Chinese medicine composition tablets of the present invention

[0093] ⑴. Take 320g of Codonopsis pilosula, add 9 times the weight of the medicinal material water, add 1% of cellulase, heat to 50°C, extract twice, each enzymolysis time is 1h, filter, combine the filtrates, concentrate the filtrates into a clear paste, add ethanol to make the alcohol content reach 70%, stir, let stand for 12 hours, filter, and decompress the filtrate to concentrate it into a dry paste powder to obtain Codonopsis pilosula extract;

[0094] ⑵, take 370g of polygonatum, add 10 times the weight of water, heat and decoct twice, each decoction time is 1h, filter, combine the filtrates, concentrate the filtrates to a polygonatum extract paste with a relative density of 1.15 (60°C), select AB-8 macroporous resin, the ratio of the amount of polygonatum extract paste loaded to the amount of AB-8 resin is 0.3, the mass concentration of the loaded polygonatum extract is 1.1mg / ml, the equilibrium adsorption time is 10 hours, elute with pure water for 3 to 5 column volumes, collect the eluates of the above different concentrations of 50% ethanol-water, elute for 3 to 6 column volumes, collect the eluates, and concentrate to obtain the polygonatum extract;

[0095] ⑶, take 80g of Panax notoginseng, crush it into particles with a mesh size of 20, reflux with 80% ethanol, add 10 times the weight of the medicinal material ethanol, extract twice, each decoction time is 0.5 hour, filter, combine the filtrates, and concentrate under reduced pressure to obtain Panax notoginseng concentrate; apply D101 macroporous resin to the concentrate, rinse with water for 3 to 5 column volumes, then rinse with 40% ethanol for 4 to 6 column volumes, elute with 70% ethanol for 3 to 6 column volumes, collect the Panax notoginseng eluate, concentrate and dry, and obtain the Panax notoginseng extract;

[0096] (4) Grind 50g of amber into 100-200nm fine powder by ultrafine grinding;

[0097] ⑸. Take 180g of Nardostachys serrata, add 10 times the weight of water, extract twice, decoct for 1.5 hours each time, steam distill for 1.5 hours, collect Nardostachys volatile oil, combine the above Nardostachys serrata extract filtrate, decompress and concentrate to a clear paste, add 2% chitosan by mass, heat and stir at 55°C, refrigerate and stand for 12 hours, filter, spray dry the filtrate to a dry paste powder, sieve to obtain Nardostachys serrata extract;

[0098] (6) Take the Codonopsis pilosula extract in step (1), the Polygonatum sibiricum extract in step (2), the Panax notoginseng extract in step (3), the amber ultrafine powder in step (4), and the Nardostachys grandiflora extract in step (5), mix them evenly, spray Nardostachys grandiflora volatile oil into them, add starch, substituted hydroxypropyl cellulose, magnesium stearate, and starch slurry, mix evenly, granulate, and press into tablets.

[0099] Example 5 Preparation of the Chinese medicine composition granules of the present invention

[0100] ⑴, take 320g of Codonopsis pilosula, add 10 times the weight of the medicinal material water, add 1.2% of cellulase, heat to 45°C, extract twice, each enzymolysis time is 0.5h, filter, combine the filtrates, concentrate the filtrates into a clear paste, add ethanol to make the alcohol content reach 65%, stir, let stand for 12 hours, filter, and decompress the filtrate to concentrate it into a dry paste powder to obtain Codonopsis pilosula extract;

[0101] ⑵, take 370g of polygonatum, add 9 times the weight of water, heat and decoct twice, each decoction interval is 1h, filter, combine the filtrates, and concentrate the filtrates to a polygonatum extract paste with a relative density of 1.20 (60°C), select AB-8 macroporous resin, the ratio of the amount of polygonatum extract paste loaded to the amount of AB-8 resin is 0.3-0.5, the mass concentration of the loaded polygonatum extract is 0.9mg / ml, the equilibrium adsorption time is 10 hours, elute with pure water for 3-5 column volumes, collect the eluates of the above different concentrations of 60% ethanol-water, elute for 3-6 column volumes, collect the eluates, and concentrate to obtain the polygonatum extract;

[0102] ⑶, take 80g of Panax notoginseng, crush it into 20 mesh particles, reflux with 80% ethanol, add 10 times the weight of the medicinal material ethanol, extract twice, each decoction time is 1 hour, filter, combine the filtrates, and concentrate under reduced pressure to obtain Panax notoginseng concentrate; apply D101 macroporous resin to the concentrate, rinse with water for 3 to 5 column volumes, then rinse with 30% ethanol for 4 to 6 column volumes, elute with 70% ethanol for 3 to 6 column volumes, collect the Panax notoginseng eluate, concentrate and dry, and obtain Panax notoginseng extract;

[0103] (4) Grind 50g of amber into 100-200nm fine powder by ultrafine grinding;

[0104] ⑸. Take 180g of Nardostachys serrata, add 10 times the weight of water, extract twice, decoct for 1.5 hours each time, steam distill for 1 hour, collect Nardostachys volatile oil, combine the above Nardostachys serrata extract filtrate, decompress and concentrate to a clear paste, add 2% chitosan by mass, heat and stir at 55°C, refrigerate and stand for 12 hours, filter, spray dry the filtrate to a dry paste powder, sieve to obtain Nardostachys serrata extract;

[0105] (6) Take the Codonopsis pilosula extract in the above step (1), the Polygonatum sibiricum extract in step (2), the Panax notoginseng extract in step (3), the amber ultrafine powder in step (4), and the Nardostachys grandiflora extract in step (5), mix them evenly, spray Nardostachys grandiflora volatile oil, add dextrin, starch, lactose, sodium carboxymethyl starch, mix evenly, granulate, dry, and mix evenly to make granules.

[0106] Comparative Example 1 Preparation of Wenxin Granules of the Present Invention (Closest to the Prior Art CN01131734.5)

[0107] According to the present invention, the preparation is carried out in accordance with the most similar prior art CN01131734.5, and the specific scheme is as follows:

[0108] Take 300g of Codonopsis pilosula, 400g of Polygonatum sibiricum, 60g of Panax notoginseng, 40g of Amber, and 200g of Nardostachys grandiflora;

[0109] Preparation method: The above five flavors and amber are crushed into fine powder, and the volatile oil is extracted from nard. The aqueous solution after extraction is collected in another container; Panax notoginseng is crushed into coarse powder, extracted twice with 80% ethanol reflux, each time for 2 hours, filtered, the filtrates are combined, and concentrated under reduced pressure to a suitable clear paste, the residues are decocted with water twice, the first time for 2 hours and the second time for 1.5 hours, and the decoctions are combined: Codonopsis pilosula and Polygonatum sibiricum are decocted with water twice, the first time for 2 hours and the second time for 1.5 hours, the decoctions are combined with the above decoctions and filtered; the filtrate is concentrated to a clear paste with a relative density of 1.20-1.30 (60°C), ethanol is added to make the alcohol content reach 65%, stirred, allowed to stand for 24 hours, filtered, the filtrate is concentrated under reduced pressure to a suitable thick paste, combined with the Panax notoginseng clear paste, and mixed. Add the above-mentioned amber fine powder, 518 g of sucrose, 100 g of beta-cyclodextrin, 2.47 g of aspartame, and an appropriate amount of dextrin, mix well, granulate, dry, spray with nard volatile oil, mix well, and make 1000 g of granules.

[0110] The content of the granules prepared by the preparation method of the best embodiment 1 of the present invention and the granules prepared by the method of comparative example 1 of the present invention (closest to the prior art CN01131734.5) are compared. The content determination can refer to the detection method in the relevant patent application 202210084515.9, and is calculated based on the total amount of notoginseng saponin R1 (C47H80O18), ginsenoside Rg1 (C42H72O14) and ginsenoside Rb1 (C54H92O23). The chromatographic conditions are acetonitrile as mobile phase A and water as mobile phase B, and the gradient elution program is: at 0-12min, the volume ratio of mobile phase A is 16→19%, and the volume ratio of mobile phase B is 84→81%; at 12-35min, the volume ratio of mobile phase A is 19→24%, and the volume ratio of mobile phase B is 81→76%; at 35-38min, the volume ratio of mobile phase A is 24→28%, and the volume ratio of mobile phase B is 76→72%; at 38-60min, the volume ratio of mobile phase A is 28→31%, and the volume ratio of mobile phase B is 72→69%; at 60-70min, the volume ratio of mobile phase A is 31→43%, and the volume ratio of mobile phase B is 69→57%; the temperature of the detection column is 20-30°C, and the detection wavelength is 203nm. The theoretical plate number should be not less than 2000 calculated based on the ginsenoside Rg1 peak. The specific content determination indicators are as follows.

[0111] Table 5 Comparison of the content of the granules of the present invention and the closest prior art drug

[0112]

[0113] It can be seen from the results in Table 5 that the Chinese medicine composition prepared by the present invention has further enrichment and improvement in the content of effective ingredients compared with the medicine in Comparative Example 1, especially in the content of total saponins, total polysaccharides of polygonatum, total polysaccharides of codonopsis pilosula, total flavonoids of naringa, etc., which are significantly improved.

[0114] Test Example 1 Antiarrhythmic Pharmacological Experiment of the Chinese Medicine Composition of the Present Invention

[0115] 1 Experimental Materials

[0116] 1.1 Drugs and reagents

[0117] The Chinese medicine composition of the present invention is a medicine prepared according to the method of Example 1 of the present invention,

[0118] ⑴. Take 300g of Codonopsis pilosula, add 10 times the weight of water, add 1% of cellulase, heat to 50°C, extract twice, each enzymolysis time is 1h, filter, combine the filtrates, concentrate the filtrates into a clear paste, add ethanol to make the alcohol content reach 70%, stir, let stand for 12 hours, filter, and decompress the filtrate to concentrate it into a dry paste powder to obtain Codonopsis pilosula extract;

[0119] ⑵, take 400g of polygonatum, add 10 times the weight of water, heat and boil twice, each boiling interval is 1h, filter, combine the filtrates, concentrate the filtrates to a relative density of 1.10-1.30 (60℃), select AB-8 macroporous resin, the ratio of the amount of polygonatum extract to the amount of AB-8 resin is 0.4, the mass concentration of the polygonatum extract is 1mg / ml, the equilibrium adsorption time is 10 hours, and 3-5 column volumes are eluted with pure water, and 60% is collected. Ethanol-Water The eluents of different concentrations are eluted for 5 column volumes, and the eluents are collected and concentrated to obtain the polygonatum sibiricum extract;

[0120] ⑶, take 60g of Panax notoginseng, crush it into 20 mesh particles, reflux with 80% ethanol, add 10 times the weight of the medicinal material ethanol, extract twice, each decoction time is 1 hour, filter, combine the filtrates, and concentrate under reduced pressure to obtain Panax notoginseng concentrate; apply D101 macroporous resin to the concentrate, rinse with water for 4 column volumes, then rinse with 30% ethanol for 6 column volumes, elute with 60% ethanol for 6 column volumes, collect the Panax notoginseng eluate, concentrate and dry, and obtain the Panax notoginseng extract;

[0121] (4) Grind 40g of amber into 100-200nm fine powder by ultrafine grinding;

[0122] ⑸. Take 200g of Nardostachys serrata, add 9 times the weight of the medicinal material water, extract twice, decoct for 1 hour each time, steam distill for 1.5 hours, collect the volatile oil of Nardostachys serrata, combine the above Nardostachys serrata extract filtrate, decompress and concentrate to a clear paste, add 2% chitosan by mass, heat and stir at 55°C, refrigerate and stand for 12 hours, filter, spray dry the filtrate to a dry paste powder, sieve to obtain Nardostachys serrata extract;

[0123] (6) Take the Codonopsis pilosula extract in step (1), the Polygonatum sibiricum extract in step (2), the Panax notoginseng extract in step (3), the amber ultrafine powder in step (4), and the Nardostachys grandiflora extract in step (5), mix them evenly, spray in Nardostachys grandiflora volatile oil, add appropriate amounts of beta-cyclodextrin, aspartame, and dextrin, granulate, and dry to form granules.

[0124] Positive control group drug: propafenone, 50 mg / tablet, the control group drug is prepared by the preparation method in Example 1 of Patent 01131734.5, called 01131734.5 group; saline group: 0.9% normal saline, barium chloride (prepared to a concentration of 5%), chloral hydrate (prepared to a concentration of 10%).

[0125] 1.2 Experimental instruments

[0126] Electronic balance: provided by Shanghai Tianping Instrument Factory and Science and Technology Experiment Center; Powerlab multi-channel physiological recorder.

[0127] 1.3 Experimental animals and groups

[0128] 40 healthy adult Wistar rats, male or female, with a body weight of (200±20) g, were purchased from the Experimental Animal Center of Shaanxi University of Chinese Medicine (changed to: commercially available). The 40 rats were randomly divided into 4 groups, 10 rats in each group, namely the normal control group (normal saline), the positive control group (propafenone), the 01131734.5 group, and the Chinese medicine composition group of the present invention.

[0129] 1.4 Experimental methods

[0130] After the experimental rats were adapted to feeding for 2-3 days, the dosage of each group was 110 mg kg －1 , positive control group (dose 50 mg·kg －1 )、01131734.5 group (dose 426 mg·kg －1 ), the intragastric dose of the Chinese medicine composition group of the present invention is 213 mg·kg －1. Each experimental group of rats was gavaged once a day for 7 consecutive days. 30 minutes after waiting for the last drug administration of the experiment, 10% chloral hydrate at a dose of 250 mg / kg was injected intraperitoneally to anesthetize the rats, and they were fixed on the mouse board in a supine position, and then connected to the multi-lead electrophysiological instrument on the surface of the body to record the II lead electrocardiogram of the experimental rats. After the rats were anesthetized for 30 minutes, 0.5% barium chloride solution was quickly injected into the sublingual vein at a dose of 4 mg / kg, and the injection was completed within 5 seconds as much as possible. From now on, the II lead electrocardiogram was recorded to observe the time of occurrence and duration of arrhythmia in each group of rats.

[0131] 2 Experimental test results

[0132] 2.1 Effects of barium chloride on ventricular fibrillation in rats

[0133] Table 6 Effects of each group of drugs on ventricular fibrillation induced by barium chloride in rats

[0134]

[0135] Note: Compared with the normal group, *P<0.01.

[0136] It can be seen from the experimental results in Table 6 that after one week of treatment, the rats in each experimental group, compared with the normal control group, the Chinese medicine composition group of the present invention, the 01131734.5 group and the positive control group can effectively reduce the incidence of ventricular fibrillation in rats caused by barium chloride solution, with significant differences (P<0.01). From the above description, the Chinese medicine composition group of the present invention can have obvious therapeutic and protective effects on ventricular fibrillation in rats with barium chloride, and can reduce the incidence of ventricular fibrillation in experimental rats.

[0137] 2.2 Effects of barium chloride on arrhythmias in rats

[0138] Table 7 Effects of each drug group on barium chloride-induced arrhythmia in rats

[0139]

[0140] Note: Compared with the normal group, *P<0.01; compared with the positive control drug, ■ P<0.01.

[0141] From the experimental results in Table 7, it can be seen that the positive control group (propafenone), the 01131734.5 group and the Chinese medicine composition group of the present invention can significantly delay the onset time of arrhythmia in rats caused by barium chloride solution and shorten its duration, and there is a significant difference compared with the normal control group (P < 0.01). It can be seen that compared with the 01131734.5 group, the Chinese medicine composition group of the present invention has a significant advantage in delaying the onset time of arrhythmia in rats caused by barium chloride solution and shortening its duration, which is statistically significant (P < 0.01).

[0142] In summary, the Chinese medicine composition group of the present invention can significantly delay the occurrence time of arrhythmia in rats caused by barium chloride solution and shorten its duration, which is further confirmed by the animal experimental results of the present invention. The Chinese medicine composition of the present invention achieves an effect equivalent to that of the 01131734.5 group when the dosage is reduced by half. The Chinese medicine composition of the present invention has a strong anti-arrhythmic protective effect. The effects of these pharmacological and pharmacodynamic effects are the pharmacological basis for treating arrhythmia diseases. It can be seen that the Chinese medicine composition of the present invention has outstanding beneficial effects.

Claims

1. A Chinese medicine composition for treating arrhythmia, characterized in that: The traditional Chinese medicine composition is composed of active ingredients in the following weight ratio: 28-32 parts of Codonopsis pilosula extract, 37-43 parts of Polygonatum sibiricum extract, 4-8 parts of Panax notoginseng extract, 3-5 parts of amber, and 18-22 parts of Nardostachys grandiflora extract.

2. The Chinese medicine composition according to claim 1, characterized in that The content of the codonopsis extract is ≥50%, and the active ingredients of the codonopsis extract include: a mixture of one or more ingredients of codonopsis polysaccharide, codonopsis saponin and codonopsis acetyl glucoside.

3. The Chinese medicine composition according to claim 1, characterized in that: The content of the polygonatum sibiricum extract is ≥50%, and the active ingredients of the polygonatum sibiricum extract include: a mixture of one or more ingredients of polygonatum sibiricum polysaccharide, polygonatum sibiricum saponin and polygonatum sibiricum polyphenol.

4. The Chinese medicine composition according to claim 1, characterized in that: The content of the Panax notoginseng extract is ≥60%, and the active ingredients of the Panax notoginseng extract include: a mixture of one or more components of notoginseng saponins, ginsenoside Rg1, ginsenoside Rb1, ginsenoside Rd, Panax notoginseng polysaccharides, volatile oils, amino acids, and total polysaccharides.

5. The Chinese medicine composition according to claim 1, characterized in that: The content of the nardostachys extract is ≥40%, and the active ingredients of the nardostachys extract include: a mixture of one or more ingredients of flavonoids, polysaccharides, volatile oils, triterpenes, phenols, coumarins and nardostachys ketone.

6. The Chinese medicine composition according to claim 2, characterized in that: The preparation method of the Codonopsis pilosula extract is as follows: taking Codonopsis pilosula medicinal material, adding water in an amount of 7 to 11 times the weight ratio of the medicinal material, adding cellulase in an amount of 0.05 to 1.5%, heating to a temperature of 40 to 55° C., extracting 1 to 2 times, each enzymolysis time being 0.5 to 1.5 hours, filtering, combining the filtrates, concentrating the filtrates into a clear paste, adding ethanol to make the alcohol content reach 60 to 75%, stirring, standing for 8 to 24 hours, filtering, and decompressing and concentrating the filtrate into a dry paste powder to obtain the Codonopsis pilosula extract.

7. The Chinese medicine composition according to claim 3, characterized in that: The preparation method of the polygonatum sibiricum extract is as follows: taking polygonatum sibiricum medicinal material, adding water in an amount of 8 to 12 times the weight ratio of the medicinal material, heating and decocting for 1 to 2 times, each decocting time is 0.5 to 1.5 hours, filtering, combining the filtrates, concentrating the filtrates to a polygonatum sibiricum extract paste with a relative density of 1.10 to 1.30 (60° C.), selecting AB-8 macroporous resin, the ratio of the amount of the polygonatum sibiricum extract paste loaded to the amount of the AB-8 resin is 0.3 to 0.5, the mass concentration of the loaded polygonatum sibiricum extract is 0.7 to 1.2 mg / ml, the equilibrium adsorption time is 8 to 12 hours, eluting with pure water for 3 to 5 column volumes, collecting the eluates of the above different concentrations of 40% to 60% ethanol-water, eluting for 3 to 6 column volumes, collecting the eluates, and concentrating to obtain the polygonatum sibiricum extract.

8. The Chinese medicine composition according to claim 4, characterized in that: The preparation method of the Panax notoginseng extract is as follows: taking Panax notoginseng medicinal materials, crushing them into particles with a mesh size of 20, refluxing with 75-90% ethanol, adding ethanol in an amount of 8-11 times the weight ratio of the medicinal materials, extracting 1-3 times, each decoction time is 0.5-1.5 hours, filtering, combining the filtrates, and concentrating under reduced pressure to obtain Panax notoginseng concentrated liquid; applying D101 macroporous resin to the concentrated liquid, washing with water for 3-5 column volumes, then washing with 20-40% ethanol for 4-6 column volumes, eluting with 60-80% ethanol for 3-6 column volumes, collecting the Panax notoginseng eluate, concentrating and drying, and obtaining the Panax notoginseng extract.

9. The Chinese medicine composition according to claim 3, characterized in that: The preparation method of the naringa extract comprises the following steps: taking naringa medicinal material, adding water in an amount of 8 to 12 times the weight ratio of the medicinal material, extracting for 1 to 3 times, boiling for 1 to 1.5 hours each time, steam distilling for 1 to 2 hours, collecting naringa volatile oil, combining the naringa extraction filtrate, decompressing and concentrating to a clear paste, adding chitosan with a mass fraction of 1.5 to 2.5%, heating at 55° C. and stirring evenly, refrigerating and standing for 12 hours, filtering, spray-drying the filtrate to a dry paste powder, sieving, and obtaining the naringa extract.

10. The method for preparing the Chinese medicine composition according to claim 1, characterized in that: The preparation method comprises the following steps: ⑴. Take Codonopsis pilosula, add 7-11 times the weight of the medicinal material water, add 0.05-1.5% of cellulase, heat to 40-55°C, extract 1-2 times, each enzymolysis time is 0.5-1.5h, filter, combine the filtrates, concentrate the filtrates into a clear paste, add ethanol to make the alcohol content reach 60-75%, stir, let stand for 8-24 hours, filter, and decompress the filtrate to concentrate it into a dry paste powder to obtain Codonopsis pilosula extract; ⑵, take polygonatum sibiricum medicinal material, add 8 to 12 times of water in weight ratio of medicinal material, heat and decoct for 1 to 2 times, each decoction interval is 0.5 to 1.5 hours, filter, combine the filtrates, concentrate the filtrates to a polygonatum sibiricum extract paste with a relative density of 1.10 to 1.30 (60°C), select AB-8 macroporous resin, the ratio of the amount of polygonatum sibiricum extract paste loaded to the amount of AB-8 resin is 0.3 to 0.5, the mass concentration of the loaded polygonatum sibiricum extract is 0.7 to 1.2 mg / ml, the equilibrium adsorption time is 8 to 12 hours, elute with pure water for 3 to 5 column volumes, collect the eluates of the above different concentrations of 40% to 60% ethanol-water, elute for 3 to 6 column volumes, collect the eluates, and concentrate to obtain the polygonatum sibiricum extract; ⑶. Grind the Radix Notoginseng into 20-mesh particles, reflux with 75-90% ethanol, add 8-11 times the weight of the Radix Notoginseng, extract 1-3 times, decoct for 0.5-1.5 hours each time, filter, combine the filtrates, and concentrate under reduced pressure to obtain a Radix Notoginseng concentrate; apply D101 macroporous resin to the concentrate, rinse with water for 3-5 column volumes, then rinse with 20-40% ethanol for 4-6 column volumes, elute with 60-80% ethanol for 3-6 column volumes, collect the Radix Notoginseng eluate, concentrate and dry, and obtain a Radix Notoginseng extract; (4) Ultrafine grinding of amber into fine powder of 100-200 nm; ⑸. Take the medicinal material of Nardostachys grandiflora, add 8 to 12 times the weight of the medicinal material of water, extract 1 to 3 times, each decoction time is 1 to 1.5 hours, steam distill for 1 to 2 hours, collect the volatile oil of Nardostachys grandiflora, combine the above Nardostachys grandiflora extraction filtrate, decompress and concentrate to a clear paste, add 1.5 to 2.5% chitosan by mass fraction, heat and stir evenly at 55°C, refrigerate and stand for 12 hours, filter, spray dry the filtrate to a dry paste powder, sieve, and obtain the Nardostachys grandiflora extract; (6) Take the Codonopsis pilosula extract in step (1), the Polygonatum sibiricum extract in step (2), the Panax notoginseng extract in step (3), the amber ultrafine powder in step (4), the Nardostachys grandiflora extract and volatile oil in step (5), mix them well, and add pharmaceutical excipients to prepare various oral preparations.

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